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Polyamines are essential in plague biofilm formation.
Author(s) -
Patel Chandra,
Wortham Brian,
Fetherston Jacqueline,
Perry Robert,
Oliveira Marcos
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb46-b
Subject(s) - biofilm , polyamine , microbiology and biotechnology , bacteria , biology , yersinia pestis , mutant , ornithine decarboxylase , putrescine , gene , biochemistry , chemistry , enzyme , virulence , genetics
Inhibition of polyamine biosynthetic and transport genes in bacteria has shown promising antibacterial effects. Here we report a novel role for polyamines in the biofilm formation of Yersinia pestis , the causative agent of plague. According to the CDC, biofilm is associated with 65% of human bacterial infections and has been implicated in the resistance of bacteria to antimicrobial treatments. Methods Polyamine deficient mutants of Y. pestis were generated with a single or double deletion in genes speA and speC , coding for arginine (ADC) and ornithine (ODC) decarboxylase, respectively. Polyamine levels were characterized by HPLC‐MS and biofilm by crystal violet staining and confocal laser microscopy. The mutants were genetically and chemically complimented. Polyamine pathway inhibitors were tested to chemically reproduce the biofilm deficiency. Results The polyamine putrescine was depleted progressively with the highest levels found in Y. pestis KIM6+ followed by Δ speC , Δ speA and Δ speA Δ speC . Biofilm reduction correlated with the depletion of polyamines. Mutants could be genetically rescued by gene speA or chemically by putrescine. Over expression of HmsT, an enzyme involved in biofilm formation, did not recover normal biofilm levels. The polyamine analogues proved to be bacteriocidal with MICs ranging from 0.78 μg/ml to 6.25 μg/ml. Conclusions We demonstrate that polyamines are essential for biofilm formation in Y. pestis . The high degree of sequence conservation of polyamine biosynthetic genes among pathogenic bacteria, including P. aeruginosa , V. cholerae , and S. aureus , suggests these genes may be a target in bacteria where pathogenesis is associated with biofilm. Supported by AACP and SERCEB to MAO.